In this proposal, our team of biobehavioral pain researchers joins with the Johns Hopkins Hospital team of adult SCD researchers to address the incredible challenge of pain management in SCD. Despite tremendous individual differences in clinical outcomes among patients with SCD and the clear widespread experience of almost daily pain, very little is currently known about pain phenotypes in SCD and how these phenotypes predict clinical outcomes. Our team seeks to demonstrate that individual differences in pain phenotypes occur in SCD, that inflammatory/immune responses to pain contribute to these phenotypes, and that these pain phenotypes predict important clinical outcomes in SCD. We propose two sequential studies: Study 1 will characterize pain phenotypes using measures of mood, personality, and pain-related catastrophizing and measures of laboratory-based pain processing, including pain sensitivity and pain-evoked inflammatory/immune responses. In order to determine whether these pain phenotypes are specific to SCD, laboratory pain processing measures will be compared between African American adult SCD patients and a group of matched, healthy African American adults. In order to determine the clinical utility and predictive validity of the inflammatory/immune response elicited in the laboratory, level of inflammation and immune response during a vaso-occlusive crisis (VOC) requiring hospital care will be examined in the SCD patients. Study 2 will determine whether pain phenotypes prospectively predict clinical outcomes in SCD. Measures of clinical outcome will include average daily pain, frequency and severity of VOC, and unscheduled use of health care for pain management. Medical record data for participants in Study 2 who are admitted to the Johns Hopkins Hospital Sickle Cell Infusion Center for the management of VOC will be examined to determine opioid responsivity. The ability to identify standardized measures, such as pain sensitivity, pain-evoked inflammatory/immune responses, and psychosocial factors, that help explain patients' clinical course, and especially their responses to opioid therapy, will have a dramatic effect on how health care providers approach pain management in these patients.